4-甲基-1,2,5-恶二唑-3-甲酰氯5-氧化物 | 50412-70-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 中文名称: 4-甲基-1,2,5-恶二唑-3-甲酰氯5-氧化物
• 英文名称: 4-(chlorocarbonyl)-3-methylfuroxan
• 英文别名: 4-methyl-5-oxy-furazan-3-carbonyl chloride；5-methyl-4-furoxancarboxylic acid chloranhydride；3-Methyl-4-furoxancarbonylchlorid；1,2,5-Oxadiazole-3-carbonyl chloride, 4-methyl-, 5-oxide；4-methyl-5-oxido-1,2,5-oxadiazol-5-ium-3-carbonyl chloride
• CAS: 50412-70-9
• 化学式: C₄H₃ClN₂O₃
• 分子量: 162.532
• InChiKey: OZAVDEBYBXEXHR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  10
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  68.6
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090

反应信息

• 作为反应物：
  描述：

  4-甲基-1,2,5-恶二唑-3-甲酰氯5-氧化物 、 6-氨基-3,3-二甲基-7-氧代-4-硫杂-1-氮杂双环[3.2.0]庚烷-2-羧酸 在 碳酸氢钠 作用下， 以 水 、 丙酮 为溶剂， 生成 6β-(4-methyl-5-oxy-furazan-3-carbonylamino)-penicillanic acid
  参考文献：
  名称：

  Gasco; Mortarini; Serafino, Farmaco, Edizione Scientifica, 1975, vol. 30, # 11, p. 900 - 903

  摘要：

  DOI：
• 作为产物：
  描述：

  4-甲基-5-氧基呋咱-3-羧酸 在 氯化亚砜 作用下， 生成 4-甲基-1,2,5-恶二唑-3-甲酰氯5-氧化物
  参考文献：
  名称：

  研究一些呋喃烷衍生物作为潜在的NO供体的合成和心血管活性。

  摘要：

  设计了一系列结合了呋喃喃和尼可地尔部分的杂合分子，作为具有心血管和脑血管活性的潜在NO供体。通过常规方法成功合成了36个目标分子，并通过红外光谱，1H-NMR光谱和高分辨率质谱进行了表征。测试了这些化合物对KCl诱导的内皮剥落的兔胸主动脉收缩的作用。发现有8种化合物在10 microM时可减少KCl诱导的收缩超过30％。这些化合物之一以外的所有化合物的特征在于，在苯环中存在通过酰胺或酯键与呋喃喃部分连接的吸电子基团。末端羰基键（酯或酰胺）的性质以及桥接两个羰基官能团的烷基链的长度或类型对活性几乎没有影响。测试了一种活性化合物N-（4-甲氧基-苯甲酰基）-N'-[3-甲基呋喃基-4-羰基）哌嗪（17i）在1.5 mg / kg时对麻醉大鼠的降压作用，并发现逐渐和持续的降压作用。结果表明，呋喃根-尼可地尔衍生物是设计用于高血压的NO供体化合物的有用线索。

  DOI：

  10.1248/cpb.48.808

文献信息

• Efficient assembly of mono- and bis(1,2,4-oxadiazol-3-yl)furoxan scaffolds via tandem reactions of furoxanylamidoximes
  作者：Leonid L. Fershtat、Ivan V. Ananyev、Nina N. Makhova

  DOI：10.1039/c5ra07295f

  日期：——

  effective one-pot protocol for the synthesis of new types of heterocyclic systems incorporating mono- and bis(1,2,4-oxadiazol-3-yl)furoxan cores based on the tandem heterocyclization of furoxanylamidoximes with various aliphatic, aromatic, and heterocyclic carboxylic acid chlorides under very mild conditions (Cs2CO3, MeCN, 20 °C) has been developed. In addition, a solvent-free approach for the (1,2,4-oxadiazol-3-yl)furoxan

  一种通用，简便，高效的一锅操作规程，用于基于呋喃西酰胺基肟与各种脂肪族化合物的串联杂环化反应，合成掺入单和双（1,2,4-恶二唑-3-基）呋喃核的新型杂环系统，已经开发了在非常温和的条件下（Cs 2 CO 3，MeCN，20°C）的芳族和杂环羧酸氯化物。此外，已经实现了一种无溶剂的方法，该方法用于通过呋喃酰胺基肟与Sc（OTf）3催化的原甲酸三甲酯反应合成（1,2,4-恶二唑-3-基）呋喃。步骤经济和作用范围的优势使这些反应成为组装具有通用化学和生物医学兴趣的杂环支架的强大工具。
• NOBF4-Mediated Assembly of the Sydnone Imine Scaffold in the Synthesis of Double Nitric Oxide Donors
  作者：Leonid L. Fershtat、Alexander D. Shuvaev、Egor S. Zhilin

  DOI：10.1055/a-2011-7264

  日期：——

  step was developed. The described protocol excludes the isolation of carcinogenic N-nitrosamines, operates broad substrate scope, and enables the preparation of fully substituted sydnone imines linked to the furoxan ring via different linkers or directly through C–C bond. Synthesized library of furoxan-sydnone imine hybrids demonstrated a promising ability to release NO in a wide range of concentrations

  开发了一种直接构建呋喃-苯酮亚胺双 NO-供体的方法，该方法涉及 NOBF 4介导的 α-氨基腈的亚硝化-环化序列作为关键合成步骤。所描述的协议不包括致癌性N -nitrosamines的分离, 操作范围广泛, 并能够通过不同的连接器或直接通过 C-C 键连接到呋喃环的完全取代的 sydnone 亚胺。合成的呋喃-苯酮亚胺杂化物库展示了在广泛浓度范围内释放 NO 的有前途的能力，这对各种生物医学见解很有用。
• 2-Phenyl-substituierte Imidazotriazinone als Phoshodiesterase Inhibitoren
  申请人：Bayer Pharma Aktiengesellschaft

  公开号：EP1174431B1

  公开（公告）日：2012-05-30
• Synthesis, characterization, and biological evaluation of furoxan coupled ibuprofen derivatives as anti-inflammatory agents
  作者：Mohd Amir、Mohd Wasim Akhter、Ozair Alam

  DOI：10.1007/s00706-015-1557-x

  日期：2016.3

  A series of furoxan-based nitric oxide releasing ibuprofen derivatives were synthesized and tested for their anti-inflammatory, analgesic, ulcerogenic, lipid peroxidation, and hepatotoxic properties. The compounds exhibited more protection than ibuprofen with regard to gastric toxicity. Among the tested compounds 4-[2-[2-(4-isobutylphenyl)propanamido] ethoxycarbonyl]-3-methylfuroxan and 4-[2-[2-(4-isobutylphenyl)propanoyl]hydrazinecarbonyl]-3-phenylfuroxan emerged as most active anti-inflammatory agents with reduced gastrotoxicity. The results showed that incorporation of NO donating group caused a moderate increase in anti-inflammatory activity with a marked decrease in gastric ulcerations compared to their parent drug ibuprofen. A molecular docking study of all the compounds was also performed to provide the binding modes of COX-1 enzyme. Among all the titledcompounds, 4-[2-[2-(4isobutylphenyl)propanamido]ethoxycarbonyl]-3-methylfuroxan was found to be most potent and have high docking score showing favorable orientation within the COX-1 binding site.
• New 1,4-Dihydropyridines Conjugated to Furoxanyl Moieties, Endowed with Both Nitric Oxide-like and Calcium Channel Antagonist Vasodilator Activities
  作者：Antonella Di Stilo、Sonja Visentin、Clara Cena、Andrea Marcello Gasco、Giuseppe Ermondi、Alberto Gasco

  DOI：10.1021/jm9803267

  日期：1998.12.1

  A series of 4-phenyl-1,4-dihydropyridines substituted at the ortho and meta positions of the phenyl ring with NO-donating furoxan moieties and their non-NO-releasing furazan analogues were synthesized and pharmacologically characterized. The vasodilator activities of these compounds were evaluated on rat aorta and expressed as EC50 values or as EC50iGC values when obtained in the presence of inhibitors of guanylate cyclase methylene blue (MB) and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-(ODQ). Affinities to 1,4-DHP receptors on Ca2+ channels, expressed as IC50 values, were determined through displacement experiments of [H-3]-nitrendipine on rat cortex homogenates. A linear correlation between IC50 and EC50 values was found for compounds unable to release NO. EC50calcd values for derivatives containing NO-donor moieties, expression of the Ca2+-blocking component of their vasodilator activity, were interpolated on this linear regression. They showed a good correspondence with EC50iGC values determined in the presence of soluble guanylate cyclase inhibitors. Analysis of (EC50EC50)-E-iGC/ ratios provided a useful tool to distinguish well-balanced hybrids from derivatives biased toward Ca2+-blocking or NO-dependent vasodilator activity. A detrimental effect on affinity to the 1,4-DHP receptor, due to substitution at the ortho and meta positions of the 4-phenyl ring, was observed. SAR to explain this effect is proposed.